2018-05-23T12:59:03ZTime and psychostimulants: Opposing long-term structural effects in the adult ADHD brain. A longitudinal MR studyhttp://hdl.handle.net/10230/34706
Time and psychostimulants: Opposing long-term structural effects in the adult ADHD brain. A longitudinal MR study
Pretus, Clara; Ramos Quiroga, Josep Antoni; Richaret, Vanesa; Corrales, Montse; Picado, Marisol; Carmona, Susanna; Vilarroya, Óscar
Long-term effects of psychostimulants such as methylphenidate on ADHD patients have been proved to be difficult to capture in cross-sectional studies comparing medicated and non-medicated samples and in longitudinal studies with children, with age-related maturational processes possibly confounding independent effects of medication. However, chronic psychostimulant administration at therapeutic doses has been proven to yield profound neuroadaptive changes in rodent models. Here, we present for the first time the effect of psychostimulant treatment on brain volumes in a sample of medication-naïve adult ADHD patients. We investigated grey matter volume changes in a sample of 41 medication-naïve adult ADHD patients before and after three years of psychostimulant treatment (N = 25) or no treatment (N = 16) compared to healthy adults (N = 25). We found a significant group x time interaction effect on left putamen grey matter volumes, with a decrease in left putamen volumes in the non-medicated group compared to both the medicated group and controls, and no differences between the medicated group and controls. Our results suggest a normalizing effect of psychostimulant treatment on the left putamen volume loss detected in non-medicated ADHD patients.
2017-01-01T00:00:00ZA study on the bioequivalence of lithium and valproate salivary and blood levels in the treatment of bipolar disorderhttp://hdl.handle.net/10230/34705
A study on the bioequivalence of lithium and valproate salivary and blood levels in the treatment of bipolar disorder
Murru, A.; Torra, M.; Callari, A.; Pacchiarotti, I.; Romero, S.; Gonzalez de la Presa, B.; Varo, C.; Goikolea, J.M.; Pérez Solá, Victor; Vieta, Eduard; Colom, F.
Lithium (Li) and valproate (VPA) are used in the treatment of bipolar disorder (BD), with narrow therapeutic window requiring periodic control of serum levels. This prevents intoxication, lack of efficacy due to low serum concentrations, and allows monitoring adherence. We aimed at evaluating the bioequivalence of salivary and blood levels of LI or VPA in a sample of adult BD patients. Secondarily, lithium bioequivalence was evaluated across different patients' lifespans. BD patients treated with either Li or VPA underwent contemporary standard serum and salivary measurements. Blood levels of both drugs were taken according to standard procedures. Li salivary levels were performed by an adapted potentiometric method on the AVL9180 electrolyte analyzer. VPA salivary levels were taken with an immune-assay method with turbidimetric inhibition. A total of 50 patients (38 on Li, 12 on VPA) were enrolled. Blood-saliva bioequivalence for VPA was not found due to a high variability in salivary measures. Li measures resulted in a high correlation (r=0.767, p<0.001), showing no partial correlation with age (r=0.147, p=0.380). Li salivary test is a reliable method of measuring Li availability and is equivalent to serum levels. Potential advantages of Li salivary testing are its non-invasive nature and the possibility of doing the test during the usual appointment with the psychiatrist.
2017-01-01T00:00:00ZSerotonin 2A receptor disulfide bridge integrity is crucial for ligand binding to different signalling states but not for its homodimerizationhttp://hdl.handle.net/10230/34704
Serotonin 2A receptor disulfide bridge integrity is crucial for ligand binding to different signalling states but not for its homodimerization
Iglesias, Alba; Cimadevila, Marta; de la Fuente, Rocío Ailim; Martí Solano, Maria; Cadavid, María Isabel; Castro, Marián; Selent, Jana; Loza, María I.; Brea, José
The serotonin 2A (5-HT2A) receptor is a G-protein coupled receptor (GPCR) with a conserved disulfide bridge formed by Cys148 (transmembrane helix 3, TM3) and Cys227 (extracellular loop 2, ECL-2). We hypothesized that disulfide bridges may determine serotonin 5-HT2A receptor functions such as receptor activation, functional selectivity and ligand recognition. We used the reducing agent dithiothreitol (DTT) to determine how the reduction of disulfide bridges affects radioligand binding, second messenger mobilization and receptor dimerization. A DTT-induced decrease in the number of binding sites (1190 ± 63.55 fmol/mg protein for control cells compared with 921.2 ± 60.84 fmol/mg protein for DTT-treated cells) as well as in the efficacy of both signalling pathways characterized was observed, although the affinity and potency were unchanged. Bioluminiscence resonance energy transfer (BRET) assays revealed the DTT treatment did not modify the homodimeric nature of serotonin 5-HT2A receptors. In molecular dynamic simulations, the ECL-2 of the receptor with a broken cysteine bond adopts a wider variety of conformations, some of which protrude deeper into the receptor orthosteric binding pocket leading to collapse of the pocket. A shrunken binding pocket would be incapable of accommodating lysergic acid diethylamide (LSD). Our findings suggest that the decrease of efficacy may be due to disruption of disulfide bridge between TM3 and ECL-2. This reveals the integrity of the ECL-2 epitope, which should be explored in the development of novel ligands acting as allosteric modulators of serotonin 5-HT2A receptors.
2017-01-01T00:00:00ZPatient independent representation of the detailed cardiac ventricular anatomyhttp://hdl.handle.net/10230/34703
Patient independent representation of the detailed cardiac ventricular anatomy
Paun, Bruno; Bijnens, Bart; Iles, Tinen; Iaizzo, Paul A.; Butakoff, Constantine
Reparameterization of surfaces is a widely used tool in computer graphics known mostly from the remeshing algorithms. Recently, the surface reparameterization techniques started to gain popularity in the field of medical imaging, but mostly for convenient 2D visualization of the information initially represented on 3D surfaces (e.g. continuous bulls-eye plot). However, by consistently mapping the 3D information to the same 2D domain, surface reparameterization techniques allow us to put into correspondence anatomical shapes of inherently different geometry. In this paper, we propose a method for anatomical parameterization of cardiac ventricular anatomies that include myocardium, trabeculations, tendons and papillary muscles. The proposed method utilizes a quasi-conformal flattening of the myocardial surfaces of the left and right cardiac ventricles and extending it to cover the interior of the cavities using the local coordinates given by the solution of the Laplace’s equation. Subsequently, we define a geometry independent representation for the detailed cardiac left and right ventricular anatomies that can be used for convenient visualization and statistical analysis of the trabeculations in a population. Lastly we show how it can be used for mapping the detailed cardiac anatomy between different hearts, which is of considerable interest for detailed cardiac computational models or shape atlases.
2017-01-01T00:00:00Z